GENETIC MODULATION OF CELLULAR RADIATION RESPONSES

细胞辐射反应的基因调节

• 批准号: 6376339
• 负责人: RUPERT K. SCHMIDT-ULLRICH
• 金额: $ 70.59万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6376339
• 关键词: gene therapy; ionizing radiation; neoplasm /cancer radiation therapy; radiation sensitivity

OVERALL DESCRIPTION (Applicant's Description) Gene therapeutic approaches to cancer need to consider the multi-genetic nature of the disease. Enhancement of ionizing radiation (IR) toxicity through improve understanding of molecular mechanisms of tumor cell radio- responsiveness, involving gene transfer experimentation, is the goal of this Program. It considers the complexity of cellular responses and concentrates on genes and cell functions contribution to cellular radio- sensitivity. As many cellular IR responses remain to be defined, each project has a strong mechanistic remain to be defined, each project has a strong mechanistic investigational component beyond exploring the potential of gene therapeutic application. The expression modulation of individual genes represent the most specific approach to identifying functions of genes/gene products specifically modulating cellular radio- responsiveness. The projects involve in vitro and in vivo experimentation as well as clinical investigation. The Program utilizes a spectrum of neoplastic cell, carcinomas (Projects 1-3), malignant gliomas (projects 3 and 4) and lymphomatous blasts (Project 5). Specific study topics include: (a) Receptor (EGFR)-mediated initiation of signal transduction at the plasma membrane and downstream signaling effects; (b) regulation of the cell cycle by Ca2+ and regulatory proteins; (c) Effects of ER on the modulation of the existing balance of cells between proliferative and apoptotic responses through relative differences in signals along the proliferation and stress pathways, including roles of the protein kinase C (PKC) modulator (bryostatin 1, Bryo), p53, apoptosis modifiers (Bcl-2/Ba), and manipulation of DNA synthesis (HSV-TK; (d) exploratory clinical application of the PKC modulator Bryo because of its potential of improving the effects of total body irradiation an important of autologous bone marrow transplantation. Besides the common scientific theme, the Program is further linked by common technologies provided by the adenovirus, animal/cellular assays, and administrative cores. While the genetic experimentation will elucidate specific mechanisms of cellular radio-responsiveness. Future experimentation will have to determine whether gene transfer or novel therapeutic low Mr compounds will be most effective.

总体描述（申请人的描述） 癌症的基因治疗方法需要考虑多基因 疾病的性质。电离辐射（IR）毒性的增强 通过改善对肿瘤细胞射射的分子机制的了解 涉及基因转移实验的响应能力是 这个程序。它考虑了细胞反应的复杂性和 集中于基因和细胞功能对细胞射射的贡献 灵敏度。由于许多细胞IR响应仍有待定义，每个响应仍有 项目有很强的机械尚待定义，每个项目都有一个 强大的机械研究组件探索了 基因治疗应用的潜力。表达调制的调制 单个基因代表了识别最具体的方法 基因/基因产物的功能专门调节细胞射射 响应能力。这些项目涉及体外和体内实验 以及临床研究。 该程序利用了肿瘤细胞癌（项目） 1-3），恶性神经胶质瘤（项目3和4）和淋巴爆炸 （项目5）。特定的研究主题包括：（a）受体（EGFR）介导的 在质膜和下游的信号转导开始 信号效应； （b）通过Ca2+和调节的细胞周期调节细胞周期 蛋白质； （c）ER对现有平衡调制的影响 通过相对的增殖和凋亡反应之间的细胞 沿着增殖和应力途径的信号差异， 包括蛋白激酶C（PKC）调节剂的作用（Bryostatin 1， Bryo），p53，凋亡修饰剂（BCL-2/BA）和DNA操纵 合成（HSV-TK；（D）PKC的探索性临床应用 调制器Bryo因为它具有改善总的影响的潜力 人体辐照一个自体骨髓移植的重要性。 除了共同的科学主题外，该程序还由 腺病毒，动物/细胞测定法提供的常见技术， 和行政核心。 遗传实验将阐明 蜂窝放射性响应性。未来的实验必须 确定基因转移或新型治疗低MR化合物是否会 最有效。